A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
A National Population-based Study Of Rheumatic Heart Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$877,826.00
Summary
Whilst overall a rare disease, Indigenous peoples have disproportionately high rates of rheumatic heart disease (RHD). This study explores the prevalence and distribution of RHD in pregnancy in Australia and New Zealand. It details current management, diagnostic and referral process and risk factors. Key attributes of culturally safe models of care for RHD in pregnancy are explored, particularly as they relate to Indigenous women. Findings will inform policy, guidelines and education resources.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989920
Funder
Australian Research Council
Funding Amount
$750,000.00
Summary
Microbial and Cellular Imaging and Analysis Facility. The Microbial and Cellular Imaging and Analysis Facility will rapidly establish itself as one of Australia's premier science facilities. It will provide the capacity to investigate the structure and molecular dynamics of viruses and microbial, human, animal and plant cells with unprecedented high resolution in both pure and applied research settings, guided by Australia's leading experts in many research strengths. This facility addresses a c ....Microbial and Cellular Imaging and Analysis Facility. The Microbial and Cellular Imaging and Analysis Facility will rapidly establish itself as one of Australia's premier science facilities. It will provide the capacity to investigate the structure and molecular dynamics of viruses and microbial, human, animal and plant cells with unprecedented high resolution in both pure and applied research settings, guided by Australia's leading experts in many research strengths. This facility addresses a current unmet need for scientists in this country and will provide cutting-edge technologies to Australian researchers so they can better detect, understand, and treat human, animal and plant diseases and the environmental impact of climate change.Read moreRead less
The biosynthesis of structural proteins in parasites. The socio-economic impact of parasitic diseases, in Australia and throughout the world, is enormous- they kill 2-3 million people per year and cost livestock industries billions of dollars per annum. Some are serious food and waterborne threats, such as the coccidia, because they are transmitted from person-to-person via the faecal-oral route, or via ingestion of contaminated water or food, or through the ingestion of cysts in raw or underco ....The biosynthesis of structural proteins in parasites. The socio-economic impact of parasitic diseases, in Australia and throughout the world, is enormous- they kill 2-3 million people per year and cost livestock industries billions of dollars per annum. Some are serious food and waterborne threats, such as the coccidia, because they are transmitted from person-to-person via the faecal-oral route, or via ingestion of contaminated water or food, or through the ingestion of cysts in raw or undercooked meat. They cause diarrhoea, which in some cases, can be life-threatening. We will understand how the coccidia protect themselves as they move from host to host and, through that understanding, develop new ways to control them and eliminate the suffering caused by parasitic diseases.Read moreRead less
Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. L ....Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. Leishmaniasis, recently found in Australia, is a risk for overseas travellers, livestock and wildlife. This research will provide an understanding of what makes these parasites successful, paving the way for development of novel drugs to combat these chronic diseases.Read moreRead less
Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection follo ....Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection following a single administration. The aims of this study are to investigate the immunological mechanisms underlying the protective response by this novel vaccine using bovine and murine models. This study will discover new control measures for botulism in Australia.Read moreRead less
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.